Trimethyllysine dioxygenase (TMLHE) (TMLHE)

Trimethyllysine dioxygenase (TMLHE) is a mitochondrial enzyme that catalyzes the first and rate-limiting step in the de novo biosynthesis of carnitine (UniProt, 2024). It converts epsilon-trimethyllysine into 3-hydroxy-trimethyllysine using alpha-ketoglutarate, molecular oxygen, ferrous iron, and ascorbate as cofactors (PubMed, 2012). Carnitine is essential for the transport of long-chain fatty acids into the mitochondria for beta-oxidation, making TMLHE a critical regulator of cellular energy metabolism (NCBI, 2023). Genetic deficiencies in the TMLHE gene, located on the X chromosome, have been identified as a risk factor for non-syndromic autism spectrum disorder, likely due to localized carnitine depletion in the brain (Cell, 2012). Pharmacologically, TMLHE is targeted by drugs like meldonium (Mildronate), which inhibit the enzyme to shift metabolism toward glucose oxidation, providing cardioprotective effects in ischemic conditions (DrugBank, 2024). Understanding TMLHE function is vital for addressing metabolic disorders and exploring therapeutic avenues for neurodevelopmental conditions.

Other names

Trimethyllysine hydroxylaseTMLHTMLDEpsilon-trimethyllysine 2-oxoglutarate dioxygenaseBBOX2

Competitive inhibition of trimethyllysine dioxygenase to reduce the rate of carnitine biosynthesis, thereby shifting cellular energy metabolism from fatty acid oxidation to glucose oxidation.